7C2K

COVID-19 RNA-dependent RNA polymerase pre-translocated catalytic complex

7C2K の概要

• エントリーDOI: 10.2210/pdb7c2k/pdb
• EMDBエントリー: 30275
• 分子名称: RNA-directed RNA polymerase, Non-structural protein 8, Non-structural protein 7, ... (6 entities in total)
• 機能のキーワード: covid-19, 2019-ncov, sars-cov-2, virus, rdrp, nsp12, nsp7, nsp8, rtc, cryo-em, viral protein, rna polymerase, drug target, antiviral, pre-translocated catalytic complex, viral protein-rna complex, viral protein/rna
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 177127.99

構造登録者

Wang, Q.,Gao, Y.,Ji, W.,Mu, A.,Rao, Z. (登録日: 2020-05-07, 公開日: 2020-06-03, 最終更新日: 2025-06-25)

主引用文献

Wang, Q.,Wu, J.,Wang, H.,Gao, Y.,Liu, Q.,Mu, A.,Ji, W.,Yan, L.,Zhu, Y.,Zhu, C.,Fang, X.,Yang, X.,Huang, Y.,Gao, H.,Liu, F.,Ge, J.,Sun, Q.,Yang, X.,Xu, W.,Liu, Z.,Yang, H.,Lou, Z.,Jiang, B.,Guddat, L.W.,Gong, P.,Rao, Z.
Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase.
Cell, 182:417-428.e13, 2020

PubMed Abstract: Nucleotide analog inhibitors, including broad-spectrum remdesivir and favipiravir, have shown promise in in vitro assays and some clinical studies for COVID-19 treatment, this despite an incomplete mechanistic understanding of the viral RNA-dependent RNA polymerase nsp12 drug interactions. Here, we examine the molecular basis of SARS-CoV-2 RNA replication by determining the cryo-EM structures of the stalled pre- and post- translocated polymerase complexes. Compared with the apo complex, the structures show notable structural rearrangements happening to nsp12 and its co-factors nsp7 and nsp8 to accommodate the nucleic acid, whereas there are highly conserved residues in nsp12, positioning the template and primer for an in-line attack on the incoming nucleotide. Furthermore, we investigate the inhibition mechanism of the triphosphate metabolite of remdesivir through structural and kinetic analyses. A transition model from the nsp7-nsp8 hexadecameric primase complex to the nsp12-nsp7-nsp8 polymerase complex is also proposed to provide clues for the understanding of the coronavirus transcription and replication machinery.

PubMed: 32526208
DOI: 10.1016/j.cell.2020.05.034

実験手法

ELECTRON MICROSCOPY (2.93 Å)